Ultra-High Field Measurements of Glycogen, IMCL and Perfusion in Skeletal Muscle in Post-Exercise Recovery: A ¹³C and ¹H MRS Study
Mary Charlotte Stephenson¹, Frances Gunner², Elizabeth J. Simpson², Paul Greenhaff², Susan T. Francis¹, Ian A. MacDonald², Peter G. Morris^1
1SPMMRC, School of Physics and Astronomy, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom; ²School of Biomedical Sciences, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

This study assesses the feasibility of sequentially monitoring muscle glycogen and IMCL levels, and perfusion, in exercising and non-exercising thigh muscles, prior to and following exercise at 7T. Levels of glycogen in exercising muscles decreased significantly during exercise, with larger decreases following higher intensity exercise. Carbohydrate re-feeding increased glycogen levels with levels returning towards baseline.  Levels of glycogen in the non-exercising muscles showed no change following exercise and re-feeding. No significant changes in IMCL were measured. Perfusion data indicates an increase in muscle perfusion during exercise, however further analysis will be carried out to further improve results.

Longitudinal Evaluation of Intramyocellular Lipid (IMCL) in Tibialis Anterior (TA) Muscle of Ob/ob and Ob/- Control Mice Using a Cryogenic Surface Coil at 9.4 T and Correlation with Insulin Levels
Qiong Ye^1,2, Carsten Friedrich Danzer³, Alexander Fuchs¹, Wilhelm Krek³, Markus Rudin^1,2
1Institute for Biomedical Engineering, Zürich, Switzerland; ²Institute for Pharmacology and Toxicology, Zürich, Switzerland; ³Institute of Cell Biology, Zürich, Switzerland

Progress of intramyocellular lipid (IMCL) levels in tibialis anterior (TA) was investigated with 1H MRS on mouse of obesity model and correlated with insulin levels. In this work, reproducibility of single voxel 1H MRS, spatial heterogeneity of IMCL and influence of T2 relaxation were evaluated using a cryogenic transceiver RF coil. From the results, the ratios of IMCL/tCr in TA were significantly higher in ob/ob mice than in their age-matched ob/-lean controls at all ages studied while in ob/ob mice IMCL levels increased from weeks 11 to 16, and then decreased from weeks 17 to 25, while their age-matched lean controls show stable IMCL. A close correlation between IMCL/tCr and plasma insulin levels has been observed in ob/ob mice at the ages studied.

Diffusion Tensor Imaging to Track Changes in Skeletal Muscle Architecture of Sarcopenic Rats
Ihssan S. Masad^1,2, Jacob M. Wilson³, S-R Lee³, Y-M Park³, Paul C. Henning³, Bahram H. Arjmandi³, J-S Kim³, Samuel Colles Grant^1,2
1Department of Chemical & Biomedical Engineering, The Florida State University, Tallahassee, FL, United States; ²National High Magnetic field Laboratory, Tallahassee, FL, United States; ³Department of Nutrition, Food & Exercise Sciences, The Florida State University, Tallahassee, FL, United States

Diffusion tensor imaging (DTI) has demonstrated remarkable capability to assess cross-sectional areas (CSA) and myofiber architecture in muscle. However, DTI has not been applied to the study of age-related muscle wasting, known as sacropenia, in rodents. In this work, the effects of age on CSA and anisotropy of water diffusion in muscle are studied under the influence of advanced aging in rats. Results demonstrate that the soleus CSA and ADC decrease with age until reaching a plateau at advanced time points. FA increases with age until it also plateaus. These findings indicate that DTI is sensitive to sacropenic alterations.

In Vivo Human Skeletal Muscle Glycogen Measured by Chemical Exchange Saturation Transfer (GlycoCEST) and ¹³C MRS at 7T
Theodore Towse^1,2, Adienne Dula^1,2, Samuel Bearden³, Edward Welch¹, James Joers^1,2, Seth Smith^1,2, Bruce Damon^1,2
1Vanderbilt University Institute of Imaging Science, Nashville, TN, United States; ²Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States; ³Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, United States

CEST is a molecular imaging technique that allows indirect detection of protons associated with mobile proteins. GlycoCEST is a variant of CEST for imaging tissue glycogen, the storage form of glucose. With glycoCEST, the ¬-OH protons of glycogen are saturated, transfer the saturation to bulk water by way of chemical exchange which reduces the bulk water signal in proportion to the glycogen content. the purpose of this study was to determine the feasibility of glycoCEST imaging in human skeletal muscle at 7T. Our findings, although preliminary, suggest that glycoCEST imaging at 7T can be used to image muscle glycogen.

Comparison of in Vivo Post-Exercise PCr Recovery and Basal ATP Synthesis Flux for the Assessment of  Skeletal Muscle Mitochondrial Function
Nicole Martina Adriana van den Broek¹, Jolita Ciapaite¹, Klaas Nicolay¹, Jeanine J. Prompers^1
1Biomedical NMR, Department of Biomedical Engineering , Eindhoven University of Technology, Eindhoven, Netherlands

The interpretation of basal ATP synthesis flux (V_ATP) measured by ³¹P saturation transfer (ST) is not straightforward. In this study, post-exercise PCr recovery and ST-based V_ATP were compared in a rat model of mitochondrial dysfunction. Treatment with complex 1 inhibitor DPI induced mitochondrial dysfunction, as evidenced by a decreased oxygen consumption rate in isolated mitochondria and a decreased in vivo post-exercise PCr recovery. Interestingly, no significant difference in V_ATP was observed between DPI-treated rats and controls. This shows that ST measurements in rest do not necessarily reflect intrinsic mitochondrial function, but more likely the ATP demand of the cell.

The Effect of Two β-Alanine Dosing Protocols on Muscle Carnosine Synthesis and Washout Measured by ¹H-MR Spectroscopy
Tania Buehler¹, Trent Stellingwerff², Helen Anwander¹, Andrea Egger³, Roland Kreis¹, Chris Boesch^1
1Dept. of Clinical Research, University of Bern, Bern, Switzerland; ²Nestlé Research Center, Lausanne, Switzerland; ³Division of Endocrinology, Diabetes & Clinical Nutrition, University of Bern, Bern, Switzerland

Carnosine (ß-alanyl-L-histidine) occurs in high concentrations in skeletal muscle and contributes to the intracellular muscle buffering capacity. Chronic (~4 weeks) ß-alanine supplementation has been shown to increase muscle carnosine contents; however, the optimal ß-alanine dosing regime remains to be clarified. The time-course of muscle carnosine changes in both tibialis anterior (TA) and gastrocnemius (GA) muscles was evaluated in 31 healthy subjects by means of non-invasive ¹H-MRS over 16 weeks (8 weeks ß-alanine supplementation with two different, placebo-controlled dosage schemes, followed by 8 weeks wash-out). A clear dose-response was found, with type I fibers (TA) being more responsive [%] to loading.

T₁ Corrected Multipeak T₂*-IDEAL Gradient-Echo Imaging for the Quantification of Intermuscular Adipose Tissue
Dimitrios C. Karampinos¹, Huanzhou Yu², Ann Shimakawa², Richard B. Souza¹, Thomas M. Link¹, Xiaojuan Li¹, Sharmila Majumdar^1
1Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States; ²Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States

IDEAL gradient-echo imaging has been proposed for mapping the spatial distribution and quantifying the amount of intermuscular adipose tissue (IMAT). However, the large difference in T₁ of muscle and fat can cause significant overestimation in IDEAL fat fraction. In the present work, the use of a precalibrated T₁-corrected fat spectrum is proposed in order to remove T₁ bias in dual flip angle multi-peak T₂* muscle IDEAL. The noise performance of the technique is compared to the single small flip angle approach. The technique is validated in a phantom and preliminary in vivo results are shown in the calf muscle.

Perfusion, BOLD and Bioenergetics Changes After Plasmid Electrotransfer in Mouse Leg Skeletal Muscle Assessed by Multiparametric Functional (Mpf-) NMR in Vivo - not available
Celine Baligand^1,2, Claire Wary^1,2, Olivier Schakman³, Helene Gilson³, Jacques C. Menard^1,2, Jean-Paul Thissen³, Pierre Georges Carlier^1,2
1NMR Laboratory, Institute of Myology, F-75651 Paris, France; ²CEA, I²BM, MIRCen, IdM NMR Laboratory, F-75651 Paris, France; ³Unite de Diabetologie et Nutrition, Universite Catholique de louvain, B-1200 Brussels, Belgium

In vivo gene eletcrotransfer is frequently used in muscle preclinical research. Procedures have been optimized to achieve high transgene expression level and minimize damage. However, consequences on muscle function have rarely been explored. We used  multiparametric functional (mpf-)NMR imaging and spectroscopy  to investigate perfusion, BOLD, and bioenergetics simultaneously in response to exercise after electroporation of an empty plasmid in mouse leg muscle. Important changes were found in all parameters and potential interference with therapy might have to be considered. Mpf-NMR constitutes a powerful tool for the optimization of electrotransfer protocols and the longitudinal assessment of preclinical gene therapy.

Mechanical Properties of Thigh Muscle from Childhood to Adulthood with Magnetic Resonance Elastography (MRE) Technique - not available
Laëtitia Debernard¹, Ludovic Robert², Fabrice Charleux², Sabine Fanny Bensamoun^1
1Biomécanique et Bioingénierie, UMR CNRS 6600, Université de Technologie de Compiègne, Centre de Recherches de Royallieu, Compiègne, France; ²ACRIM-Polyclinique Saint Côme, Compiègne, France

Muscle tissue is strongly solicited during all the life. The structural and functional properties of the muscle can be affected by its perpetual stretches and contractile activities but also by specific muscle pathologies. Imaging techniques can determine the muscle composition and morphological properties but no quantification of the mechanical properties is recorded with such imaging techniques. Magnetic Resonance Elastography technique is capable of giving the morphological and the mechanical parameters for the same exam, allowing a complete characterization of the muscle tissue. The purpose of this study is to characterize the Vastus Medialis muscle stiffness from childhood to adulthood.

Quantification of Fat Infiltration in Thigh and Calf Muscles in Oculopharyngeal Muscular Dystrophy: Comparison of Three MRI Methods - not available
Monika Gloor¹, Arne Fischmann², Susanne Fasler², Tanja Haas², Oliver Bieri¹, Klaus Scheffler¹, Dirk Fischer^3
1Radiological Physics, University of Basel Hospital, Basel, Switzerland; ²Neuroradiology, University of Basel Hospital, Basel, Switzerland; ³Neurology, University of Basel Hospital, Basel, Switzerland

The development of non-invasive measures of the degree and progression of muscle involvement is essential for clinical trials in oculopharyngeal muscular dystrophy (OPMD) patients. In this study, three quantitative MRI measures of muscular fat infiltration are compared with regard to applicability for longitudinal studies. A very high linear correlation is observed between fat infiltration according to the 2-point Dixon method and quantitative T₂ values (R² = 0.95). Fat infiltration according to SSFP histogram analysis exhibit a lower linear correlation with T₂ values (R² = 0.88). Dixon or T₂ mapping techniques may be promising quantitative tools to study the pattern and involvement of fat infiltration longitudinally.